Anti-inflammatory effects of trans-cinnamic acid through modulation of endothelial ICAM-1 expression and neutrophil recruitment

Natural phenolic acid compounds have been extensively studied for their anti-inflammatory properties, particularly in the context of inflammation-associated diseases. In this study, we investigated the anti-inflammatory effects of trans-cinnamic acid on neutrophil accumulation during inflammatory processes using both in vivo and in vitro approaches. For the in vivo experiments, LPS-induced pleurisy was used in mice pretreated with trans-cinnamic acid. Inflammatory parameters, including plasma leakage, leukocyte infiltration, and proinflammatory cytokine levels (IL-6 and TNF-α), were quantified in the pleural exudate. In vitro, the effects of trans-cinnamic acid on neutrophil chemotaxis toward CXCL1 were assessed using the Boyden chamber assay. Additionally, human endothelial EA.hy926 cells were stimulated with TNF-α to evaluate neutrophil adhesion and the expression of the adhesion molecule ICAM-1 following trans-cinnamic acid treatment. Pretreatment with trans-cinnamic acid significantly inhibited LPS-induced pleurisy in mice by reducing protein-rich exudate formation, neutrophil infiltration, and local concentrations of TNF-α and IL-6. In vitro, trans-cinnamic acid did not alter CXCL1-induced neutrophil chemotaxis, nor the secretion of CXCL8 produced by TNF-α-stimulated EA.hy926 cells. However, it markedly reduced neutrophil adhesion to TNF-α-activated EA.hy926 cells. This reduction was associated with the downregulation of ICAM-1 expression at both the mRNA and protein levels. Overall, these findings demonstrated that trans-cinnamic acid exerted anti-inflammatory effects by inhibiting vascular permeability and leukocyte recruitment, particularly through the suppression of ICAM-1-mediated neutrophil adhesion to endothelial cells. These results support trans-cinnamic acid as a promising candidate for the development of new therapeutic agents targeting inflammatory diseases.